Fluoro and sulphonylamino containing 3,6-disubstituted azabicyclo (3.1.0) hexane derivatives as muscarinic receptor antagonists

Abstract

This invention generally relates to the derivatives of novel 3,6 disubstituted azabicyclo[3.1.0] hexane's. The compounds of this invention are MUSCARINIC receptor antagonists which are useful, inter-ail for the treatment of various diseases of the respiratory, urinary and gastrointestinal systems mediated through MUSCARINIC receptors. The invention also relates to processes for the preparation of the compounds of the invention, pharmaceutical compositions containing the compounds of the present invention and the methods of treating the diseases mediated through MUSCARINIC receptors.

1. A compound having the structure of Formula I 
       
         
           
           
               
               
           
         
       
       and its pharmaceutically acceptable salts, pharmaceutically acceptable enantiomers, diastereomers, N-oxides, wherein
 Ar represents an aryl ring which may be unsubstituted or substituted by one to three substituents independently selected from lower alkyl (C 1 -C 4 ), lower perhalo alkyl (C 1 -C 4 ), cyano, hydroxy, nitro, lower alkoxy (C 1 -C 4 ), lower perhalo alkoxy (C 1 -C 4 ), unsubstituted amino, N-lower alkyl (C 1 -C 4 ) amino or N-lower alkyl (C 1 -C 4 ) amino carbonyl; 
 R 1  represents a hydrogen, hydroxy, hydroxymethyl, amino, alkoxy, carbamoyl or halogen (fluorine, chlorine, bromine or iodine); 
 R 2  represents a C 3 -C 7  cycloalkyl ring in which from 1 to 4 hydrogen atoms are substituted with fluorine atoms, amides or sulphonamide derivatives;
 W represents (CH 2 ) p , where p represents 0 or 1; 
 X represents no atom; 
 Y represents (CH 2 ) q  wherein q represents 0; 
 Z represents oxygen, sulphur or NR 10 , wherein R 10  represents hydrogen or C 1-6  alkyl; 
 Q represents (CH 2 ) n  wherein n represents 1 to 4, or CHR 8  wherein R 8  represents H, OH, C 1-6 , alkyl, alkenyl, alkoxy, or CH 2 CHR 9  wherein R 9  represents H, OH, lower alkyl (C 1 -C 4 ) or lower alkoxy (C 1 -C 4 ); 
 
 R 6  and R 7  are independently selected from H, CH 3 , COOH, CONH 2 , NH 2  or CH 2 NH 2 ; and 
 R 4  represents a C 1 -C 15  saturated or unsaturated aliphatic hydrocarbon group in which from 1 to 6 hydrogen atoms may be substituted with the group independently selected from halogen, arylalkyl, arylalkenyl, heteroarylalkyl or heteroarylalkenyl having 1 to 2 hetero atoms selected from the group consisting of nitrogen, oxygen and sulphur atoms with an option that any 1 to 3 hydrogen atoms on the ring in said arylalkyl, arylalkenyl, hetero arylalkenyl group may be substituted with lower alkyl (C 1 -C 4 ), lower perhalo alkyl (C 1 -C 4 ), cyano, hydroxyl, nitro, lower alkoxycarbonyl, halogen, lower alkoxy (C 1 -C 4 ), lower perhaloalkoxy (C 1 -C 4 ), unsubstituted amino, N-lower alkylamino (C 1 -C 4 ) or N-lower alkylamino carbonyl (C 1 -C 4 ). 
 
     
     
       2. The compound of  claim 1 , wherein the compound has the structure of Formula II, 
       
         
           
           
               
               
           
         
       
       wherein
 Ar represents an aryl which may be unsubstituted or substituted by one to three substituents independently selected from lower alkyl (C 1 -C 4 ), lower perhalo alkyl (C 1 -C 4 ), cyano, hydroxy, nitro, lower alkoxy (C 1 -C 4 ), lower perhalo alkoxy (C 1 -C 4 ), unsubstituted amino, N-lower alkyl (C 1 -C 4 ) amino or N-lower alkyl (C 1 -C 4 ) amino carbonyl; 
 R 1  represents a hydrogen, hydroxy, hydroxymethyl, amino, alkoxy, carbamoyl or halogen (fluorine, chlorine, bromine or iodine); 
 R 2  represents a C 3 -C 7  cycloalkyl ring in which from 1 to 4 hydrogen atoms are substituted with fluorine atoms, amides or sulphonamide derivatives;
 W represents (CH 2 ) p , where p represents 0 or 1; 
 X represents no atom; 
 Y represents (CH 2 ) q  wherein q represents 0; 
 Z represents oxygen, sulphur or NR 10 , wherein R 10  represents hydrogen or C 1-6  alkyl; 
 Q represents (CH 2 ) n  wherein n represents 1 to 4, or CHR 8  wherein R 8  represents H, OH, C 1-6 , alkyl, alkenyl, alkoxy, or CH 2 CHR 9  wherein R 9  represents H, OH, lower alkyl (C 1 -C 4 ) or lower alkoxy (C 1 -C 4 ); and 
 
 R 4  represents a C 1 -C 15  saturated or unsaturated aliphatic hydrocarbon group in which from 1 to 6 hydrogen atoms may be substituted with the group independently selected from halogen, arylalkyl, arylalkenyl, heteroarylalkyl or heteroarylalkenyl having 1 to 2 hetero atoms selected from the group consisting of nitrogen, oxygen and sulphur atoms with an option that any 1 to 3 hydrogen atoms on the ring in said arylalkyl, arylalkenyl, hetero arylalkenyl group may be substituted with lower alkyl (C 1 -C 4 ), lower perhalo alkyl (C 1 -C 4 ), cyano, hydroxyl, nitro, lower alkoxycarbonyl, halogen, lower alkoxy (C 1 -C 4 ), lower perhaloalkoxy (C 1 -C 4 ), unsubstituted amino, N-lower alkylamino (C 1 -C 4 ) or N-lower alkylamino carbonyl (C 1 -C 4 ). 
 
     
     
       3. The compound of  claim 1 , wherein the compound has the structure of Formula III, 
       
         
           
           
               
               
           
         
       
       wherein
 Ar represents an aryl which may be unsubstituted or substituted by one to three substituents independently selected from lower alkyl (C 1 -C 4 ), lower perhalo alkyl (C 1 -C 4 ), cyano, hydroxy, nitro, lower alkoxy (C 1 -C 4 ), lower perhalo alkoxy (C 1 -C 4 ), unsubstituted amino, N-lower alkyl (C 1 -C 4 ) amino or N-lower alkyl (C 1 -C 4 ) amino carbonyl; 
 R 1  represents a hydrogen, hydroxy, hydroxymethyl, amino, alkoxy, carbamoyl or halogen (fluorine, chlorine, bromine or iodine); 
 R 2  represents a C 3 -C 7  cycloalkyl ring in which from 1 to 4 hydrogen atoms are substituted with fluorine atoms, amides or sulphonamide derivatives;
 Z represents oxygen, sulphur or NR 10 , wherein R 10  represents hydrogen or C 1-6  alkyl; 
 Q represents (CH 2 ) n  wherein n represents 1 to 4, or CHR 8  wherein R 8  represents H, OH, C 1-6 , alkyl, alkenyl, alkoxy, or CH 2 CHR 9  wherein R 9  represents H, OH, lower alkyl (C 1 -C 4 ) or lower alkoxy (C 1 -C 4 ); and 
 
 R 4  represents a C 1 -C 15  saturated or unsaturated aliphatic hydrocarbon group in which from 1 to 6 hydrogen atoms may be substituted with the group independently selected from halogen, arylalkyl, arylalkenyl, heteroarylalkyl or heteroarylalkenyl having 1 to 2 hetero atoms selected from the group consisting of nitrogen, oxygen and sulphur atoms with an option that any 1 to 3 hydrogen atoms on the ring in said arylalkyl, arylalkenyl, hetero arylalkenyl group may be substituted with lower alkyl (C 1 -C 4 ), lower perhalo alkyl (C 1 -C 4 ), cyano, hydroxyl, nitro, lower alkoxycarbonyl, halogen, lower alkoxy (C 1 -C 4 ), lower perhaloalkoxy (C 1 -C 4 ), unsubstituted amino, N-lower alkylamino (C 1 -C 4 ) or N-lower alkylamino carbonyl (C 1 -C 4 ). 
 
     
     
       4. The compound of  claim 1 , wherein the compound has the structure of Formula IV, 
       
         
           
           
               
               
           
         
       
       wherein R 11  is hydrogen or fluoro, R 12  is fluoro, amide or sulphonamide derivatives and s represents 1 to 2;
 R 4  represents a C 1 -C 15  saturated or unsaturated aliphatic hydrocarbon group in which from 1 to 6 hydrogen atoms may be substituted with the group independently selected from halogen, arylalkyl, arylalkenyl, heteroarylalkyl or heteroarylalkenyl having 1 to 2 hetero atoms selected from the group consisting of nitrogen, oxygen and sulphur atoms with an option that any 1 to 3 hydrogen atoms on the ring in said arylalkyl, arylalkenyl, hetero arylalkenyl group may be substituted with lower alkyl (C 1 -C 4 ), lower perhalo alkyl (C 1 -C 4 ), cyano, hydroxyl, nitro, lower alkoxycarbonyl, halogen, lower alkoxy (C 1 -C 4 ), lower perhaloalkoxy (C 1 -C 4 ), unsubstituted amino, N-lower alkylamino (C 1 -C 4 ) or N-lower alkylamino carbonyl (C 1 -C 4 );
 Z represents oxygen, sulphur or NR 10 , wherein R 10  represents hydrogen or alkyl; and 
 Q represents (CH 2 ) n  wherein n represents 1 to 4, or CHR 8  wherein R 8  represents H, OH, C 1-6 , alkyl, alkenyl, alkoxy, or CH 2 CHR 9  wherein R 9  represents H, OH lower alkyl (C 1 -C 4 ) or lower alkoxy (C 1 -C 4 ). 
 
 
     
     
       5. A compound selected from the group consisting of:
 (2R)-(1α,5α,6α)-N-[3-benzyl-3-azabicyclo[3.1.0]hexyl-6-(aminomethyl)-yl]-2-[(1R or 1S)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetamide (Compound No. 1A) 
 (2R)-(1α,5α,6α)-N-[3-benzyl-3-azabicyclo[3.1.0]hexyl-6-(aminomethyl)-yl]-2-[(1R or 1S)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetamide (Compound No. 1B) 
 (2R)-(1α,5α,6α)-N-[3-benzyl-3-azabicyclo[3.1.0]hexyl-6-(aminomethyl)-yl]-2-[(1R or 1S, 3R or 3S)-3-fluorocyclopentyl]-2-hydroxy-2-phenylacetamide (Compound No. 2) 
 (2R or 2S)-(1α,5α,6α)-N-[3-benzyl-3-azabicyclo[3.1.0]hexyl-6-(aminomethyl)-yl ]-2-[(1R or 1S)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetamide (Compound No. 3) 
 (2R or 2S)-(1α,5α,6α)-N-[3-benzyl-3-azabicyclo[3.1.0]hexyl-6-(aminomethyl)-yl ]-2-[(1R or 1S, 3R or 3S)-3-fluorocyclopentyl]-2-hydroxy-2-phenylacetamide (Compound No. 4) 
 (2R)-(1α,5α,6α)-N-[3-benzyl-3-azabicyclo[3.1.0]hexyl-6-(aminomethyl)-yl]-2-[(1R or 1S, 3R or 3S)-3-phenylacetylamino cyclopentyl]-2-hydroxy-2-phenylacetamide (Compound No. 5) 
 (2R)-(1α,5α,6α)-N-[3-benzyl-3-azabicyclo[3.1.0]hexyl-6-(aminomethyl)-yl]-2-[(1R or 1S, 3R or 3S)-3-(4-nitrophenyl) sulphonylaminocyclopentyl]-2-hydroxy-2-phenylacetamide (Compound No. 6) 
 (2R)-(1α,5α,6α)-N-[3-benzyl-3-azabicyclo[3.1.0]hexyl-6-(aminomethyl)-yl]-2-[(1R or 1S, 3R or 3S)-3-phenylsulphonylamino cyclopentyl]-2-hydroxy-2-phenylacetamide (Compound No. 7) 
 (2R)-(1α,5α,6α)-N-[3-benzyl-3-azabicyclo[3.1.0]hexyl-6-(aminomethyl)-yl]-2-[(1R or 1S, 3R or 3S)-3-benzyloxyacetylaminocyclopentyl]-2-hydroxy-2-phenylacetamide (Compound No. 8) 
 (2R)-(1α,5α,6α)-N-[3-benzyl-3-azabicyclo[3.1.0]hexyl-6-(aminomethyl)-yl]-2-[(1R or 1S, 3R or 3S)-3-(4-methoxyphenyl) sulphonylaminocyclo pentyl]-2-hydroxy-2-phenylacetamide (Compound No. 9); and 
 (2R)-(1α,5α,6α)-N-[3-benzyl-3-azabicyclo[3.1.0]hexyl-6-(aminomethyl)-yl]-2-[(1R or 1S, 3R or 3S)-3-(4-bromophenyl)sulphonylamino cyclopentyl]-2-hydroxy-2-phenylacetamide (Compound No. 10). 
 
     
     
       6. A pharmaceutical composition comprising a therapeutically effective amount of a compound of  claim 1  together with pharmaceutically acceptable carriers, excipients or diluents. 
     
     
       7. A method for treatment of an animal or human suffering from a disease or disorder of the respiratory, urinary and gastrointestinal systems, wherein the disease or disorder is mediated through muscarinic receptors, and wherein the disease or disorder is urinary incontinence, lower urinary tract symptoms (LUTS), bronchial asthma, chronic obstructive pulmonary disorders (COPD), pulmonary fibrosis, irritable bowel syndrome, obesity, diabetes and gastrointestinal hyperkinesis, the method comprising administering to said animal or human, a therapeutically effective amount of a compound having the structure of Formula I 
       
         
           
           
               
               
           
         
       
       and its pharmaceutically acceptable salts, pharmaceutically acceptable enantiomers, diastereomers, N-oxides, wherein
 Ar represents an aryl which may be unsubstituted or substituted by one to three substituents independently selected from lower alkyl (C 1 -C 4 ), lower perhalo alkyl (C 1 -C 4 ), cyano, hydroxy, nitro, lower alkoxy (C 1 -C 4 ), lower perhalo alkoxy (C 1 -C 4 ), unsubstituted amino, N-lower alkyl (C 1 -C 4 ) amino or N-lower alkyl (C 1 -C 4 ) amino carbonyl; 
 R 1  represents a hydrogen, hydroxyhydroxymethyl, amino, alkoxy, carbamoyl or halogen (fluorine, chlorine, bromine and iodine); 
 R 2  represents a C 3 -C 7  cycloalkyl ring in which from 1 to 4 hydrogen atoms are substituted with fluorine atoms, amides or sulphonamide derivatives;
 W represents (CH 2 ) p , where p represents 0 to 1; 
 X represents no atom; 
 Y represents (CH 2 ) q  wherein q represents 0; 
 Z represents oxygen, sulphur, NR 10 , wherein R 10  represents hydrogen or C 16  alkyl; 
 Q represents (CH 2 ) n  wherein n represents 1 to 4, or CHR 8  wherein R 8  represents H, OH, C 1-6 , alkyl, alkenyl, alkoxy, or CH 2 CHR 9  wherein R 9  represents H, OH, lower alkyl (C 1 -C 4 ) or lower alkoxy (C 1 -C 4 ); 
 
 R 6  and R 7  are independently selected from H, CH 3 , COOH, CONH 2 , NH 2  or CH 2 NH 2 ; and 
 R 4  represents a C 1 -C 15  saturated or unsaturated aliphatic hydrocarbon group in which from 1 to 6 hydrogen atoms may be substituted with the group independently selected from halogen, arylalkyl, arylalkenyl, heteroarylalkyl or heteroarylalkenyl having 1 to 2 hetero atoms selected from the group consisting of nitrogen, oxygen and sulphur atoms with an option that any 1 to 3 hydrogen atoms on the ring in said arylalkyl, arylalkenyl, hetero arylalkenyl group may be substituted with lower alkyl (C 1 -C 4 ), lower perhalo alkyl (C 1 -C 4 ), cyano, hydroxyl, nitro, lower alkoxycarbonyl, halogen, lower alkoxy (C 1 -C 4 ), lower perhaloalkoxy (C 1 -C 4 ), unsubstituted amino, N-lower alkylamino (C 1 -C 4 ) or N-lower alkylamino carbonyl (C 1 -C 4 ). 
 
     
     
       8. The method of  claim 7 , wherein the compound has the structure of Formula II, 
       
         
           
           
               
               
           
         
       
       wherein
 Ar represents an aryl which may be unsubstituted or substituted by one to three substituents independently selected from lower alkyl (C 1 -C 4 ), lower perhalo alkyl (C 1 -C 4 ), cyano, hydroxy, nitro, lower alkoxy (C 1 -C 4 ), lower perhalo alkoxy (C 1 -C 4 ), unsubstituted amino, N-lower alkyl (C 1 -C 4 ) amino or N-lower alkyl (C 1 -C 4 ) amino carbonyl; 
 R 1  represents a hydrogen, hydroxy, hydroxymethyl, amino, alkoxy, carbamoyl or halogen (fluorine, chlorine, bromine or iodine); 
 R 2  represents a C 3 -C 7  cycloalkyl ring in which from 1 to 4 hydrogen atoms are substituted with fluorine atoms, amides or sulphonamide derivatives;
 W represents (CH 2 ) p , where p represents 0 or 1; 
 X represents no atom; 
 Y represents (CH 2 ) q  wherein q represents 0; 
 Z represents oxygen, sulphur or NR 10 , wherein R 10  represents hydrogen or alkyl; 
 Q represents (CH 2 ) n  wherein n represents 1 to 4, or CHR 8  wherein R 8  represents H, OH, C 1-6 , alkyl, alkenyl, alkoxy, or CH 2 CHR 9  wherein R 9  represents H, OH, lower alkyl (C 1 -C 4 ) or lower alkoxy (C 1 -C 4 ; and 
 
 R 4  represents a C 1 -C 15  saturated or unsaturated aliphatic hydrocarbon group in which from 1 to 6 hydrogen atoms may be substituted with the group independently selected from halogen, arylalkyl, arylalkenyl, heteroarylalkyl or heteroarylalkenyl having 1 to 2 hetero atoms selected from the group consisting of nitrogen, oxygen and sulphur atoms with an option that any 1 to 3 hydrogen atoms on the ring in said arylalkyl, arylalkenyl, hetero arylalkenyl group may be substituted with lower alkyl (C 1 -C 4 ), lower perhalo alkyl (C 1 -C 4 ), cyano, hydroxyl, nitro, lower alkoxycarbonyl, halogen, lower alkoxy (C 1 -C 4 ), lower perhaloalkoxy (C 1 -C 4 ), unsubstituted amino, N-lower alkylamino (C 1 -C 4 ) or N-lower alkylamino carbonyl (C 1 -C 4 ). 
 
     
     
       9. The method of  claim 7 , wherein the compound has the structure of Formula III, 
       
         
           
           
               
               
           
         
       
       wherein
 Ar represents an aryl which may be unsubstituted or substituted by one to three substituents independently selected from lower alkyl (C 1 -C 4 ), lower perhalo alkyl (C 1 -C 4 ), cyano, hydroxy, nitro, lower alkoxy (C 1 -C 4 ), lower perhalo alkoxy (C 1 -C 4 ), unsubstituted amino, N-lower alkyl (C 1 -C 4 ) amino or N-lower alkyl (C 1 -C 4 ) amino carbonyl; 
 R 1  represents a hydrogen, hydroxy, hydroxymethyl, amino, alkoxy, carbamoyl or halogen (fluorine, chlorine, bromine or iodine); 
 R 2  represents a C 3 -C 7  cycloalkyl ring in which from 1 to 4 hydrogen atoms are substituted with fluorine atoms, amides or sulphonamide derivatives;
 Z represents oxygen, sulphur or NR 10 , wherein R 10  represents hydrogen or C 1-6  alkyl; 
 Q represents (CH 2 ) n  wherein n represents 1 to 4, or CHR 8  wherein R 8  represents H, OH, C 1-6 , alkyl, alkenyl, alkoxy, or CH 2 CHR 9  wherein R 9  represents H, OH, lower alkyl (C 1 -C 4 ) or lower alkoxy (C 1 -C 4 ); and 
 
 R 4  represents a C 1 -C 15  saturated or unsaturated aliphatic hydrocarbon group in which from 1 to 6 hydrogen atoms may be substituted with the group independently selected from halogen, arylalkyl, arylalkenyl, heteroarylalkyl or heteroarylalkenyl having 1 to 2 hetero atoms selected from the group consisting of nitrogen, oxygen and sulphur atoms with an option that any 1 to 3 hydrogen atoms on the ring in said arylalkyl, arylalkenyl, hetero arylalkenyl group may be substituted with lower alkyl (C 1 -C 4 ), lower perhalo alkyl (C 1 -C 4 ), cyano, hydroxyl, nitro, lower alkoxycarbonyl, halogen, lower alkoxy (C 1 -C 4 ), lower perhaloalkoxy (C 1 -C 4 ), unsubstituted amino, N-lower alkylamino (C 1 -C 4 ) or N-lower alkylamino carbonyl 1-C 4 ). 
 
     
     
       10. The method of  claim 7 , wherein the compound has the structure of Formula IV, 
       
         
           
           
               
               
           
         
       
       wherein
 R 11  is hydrogen or fluoro, R 12  is fluoro, amide or sulphonamide derivatives and s represents 1 to 2; 
 R 4  represents a C 1 -C 15  saturated or unsaturated aliphatic hydrocarbon group in which from 1 to 6 hydrogen atoms may be substituted with the group independently selected from halogen, arylalkyl, arylalkenyl, heteroarylalkyl or heteroarylalkenyl having 1 to 2 hetero atoms selected from the group consisting of nitrogen, oxygen and sulphur atoms with an option that any 1 to 3 hydrogen atoms on the ring in said arylalkyl, arylalkenyl, hetero arylalkenyl group may be substituted with lower alkyl (C 1 -C 4 ), lower perhalo alkyl (C 1 -C 4 ), cyano, hydroxyl, nitro, lower alkoxycarbonyl, halogen, lower alkoxy (C 1 -C 4 ), lower perhaloalkoxy (C 1 -C 4 ), unsubstituted amino, N-lower alkylamino (C 1 -C 4 ) or N-lower alkylamino carbonyl (C 1 -C 4 );
 Z represents oxygen, sulphur or NR 10 , wherein R 10  represents hydrogen or C 1-6  alkyl; and 
 Q represents (CH 2 ) n  wherein n represents 1 to 4, or CHR 8  wherein R 8  represents H, OH, C 1-6 , alkyl, alkenyl, alkoxy, or CH 2 CHR 9  wherein R 9  represents H, OH, lower alkyl (C 1 -C 4 ) or lower alkoxy (C 1 -C 4 ). 
 
 
     
     
       11. The method for treatment of an animal or human suffering from a disease or disorder of the respiratory, urinary and gastrointestinal systems, wherein the disease or disorder is mediated through the muscarinic receptors, and wherein the disease or disorder is urinary incontinence, lower urinary tract symptoms (LUTS), bronchial asthma, chronic obstructive pulmonary disorders (COPD), pulmonary fibrosis, irritable bowel syndrome, obesity, diabetes and gastrointestinal hyperkinesis, the method comprising administering to said animal or human a therapeutically effective amount of a pharmaceutical composition of  claim 6 . 
     
     
       12. A process of preparing a compound of Formula I 
       
         
           
           
               
               
           
         
       
       and its pharmaceutically acceptable salts, pharmaceutically acceptable enantiomers, diastereomers, N-oxides, wherein
 Ar represents an aryl which may be unsubstituted or substituted by one to three substituents independently selected from lower alkyl (C 1 -C 4 ), lower perhalo alkyl (C 1 -C 4 ), cyano, hydroxy, nitro, lower alkoxy (C 1 -C 4 ), lower perhalo alkoxy (C 1 -C 4 ), unsubstituted amino, N-lower alkyl (C 1 -C 4 ) amino or N-lower alkyl (C 1 -C 4 ) amino carbonyl; 
 R 1  represents a hydrogen, hydroxy, hydroxymethyl, amino, alkoxy, carbamoyl or halogen (fluorine, chlorine, bromine and iodine); 
 R 2  represents a C 3 -C 7  cycloalkyl ring in which from 1 to 4 hydrogen atoms are substituted with fluorine atoms, amides or sulphonamide derivatives;
 W represents (CH 2 ) p , where p represents 0 to 1; 
 X represents no atom; 
 Y represents (CH 2 ) q  wherein q represents 0; 
 Z represents oxygen, sulphur, NR 10 , wherein R 10  represents hydrogen or C 1-6  alkyl; 
 Q represents (CH 2 ) n  wherein n represents 1 to 4, or CHR 8  wherein R 8  represents H, OH, C 1-6 , alkyl, alkenyl, alkoxy, or CH 2 CHR 9  wherein R 9  represents H, OH, lower alkyl (C 1 -C 4 ) or lower alkoxy (C 1 -C 4 ); 
 
 R 6  and R 7  are independently selected from H, CH 3 , COOH, CONH 2 , NH 2  or CH 2 NH 2 ; and 
 R 4  represents a C 1 -C 15  saturated or unsaturated aliphatic hydrocarbon group in which from 1 to 6 hydrogen atoms may be substituted with the group independently selected from halogen, arylalkyl, arylalkenyl, heteroarylalkyl or heteroarylalkenyl having 1 to 2 hetero atoms selected from the group consisting of nitrogen, oxygen and sulphur atoms with an option that any 1 to 3 hydrogen atoms on the ring in said arylalkyl, arylalkenyl, hetero arylalkenyl group may be substituted with lower alkyl (C 1 -C 4 ), lower perhalo alkyl (C 1 -C 4 ), cyano, hydroxyl, nitro, lower alkoxycarbonyl, halogen, lower alkoxy (C 1 -C 4 ), lower perhaloalkoxy (C 1 -C 4 ), unsubstituted amino, N-lower alkylamino (C 1 -C 4 ) or N-lower alkylamino carbonyl (C 1 -C 4 ), comprising 
 (a) condensing a compound of Formula VI with a compound of Formula V 
 
       
         
           
           
               
               
           
         
          wherein Ar, R 1 , R 2 , W, X, Y, Z, Q, R 6  and R 7  have the same meanings as defined earlier for Formula I, to give a protected compound of Formula VII wherein Ar, R 1 , R 2 , W, X, Y, Z, Q, R 6  and R 7  are the same as defined earlier and P is a protecting group for an amino group, 
       
       
         
           
           
               
               
           
         
         (b) deprotecting the compound of Formula VII in the presence of a deprotecting agent to give an unprotected intermediate of Formula VIII wherein Ar, R 1 , R 2 , W, X, Y, Z, Q, R 6  and R 7  are the same as defined earlier, and 
       
       
         
           
           
               
               
           
         
         (c) N-alkylating or benzylating the intermediate of Formula VIII with a suitable alkylating agent or benzylating agent to give a compound of Formula I. 
       
     
     
       13. The process according to  claim 12  wherein P is any protecting group for an amino group and is selected from the group consisting of benzyl or t-butyloxy carbonyl groups. 
     
     
       14. The process according to  claim 12  wherein the reaction of a compound of Formula V with a compound of Formula VI to give a compound of Formula VII is carried out in the presence of a condensing agent which is selected from the group consisting of 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (EDC) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). 
     
     
       15. The process according to  claim 12  wherein the reaction of a compound of Formula V with a compound of Formula VI is carried out at about 0-140° C. 
     
     
       16. The process according to  claim 12  wherein the deprotection of a compound of Formula VII to give a compound of Formula VIII is carried out with a deprotecting agent which is selected from the group consisting of palladium on carbon, trifluoroacetic acid (TFA) and hydrochloric acid. 
     
     
       17. The process according to  claim 12  wherein the N-alkylation or benzylation of a compound of Formula VIII to give a compound of Formula I is carried out with a suitable alkylating or benzylating agent, L-R 4 , wherein L is any leaving group and R 4  is the same as defined earlier. 
     
     
       18. The process according to  claim 17  wherein the leaving group is selected from the group consisting of halogen, O-mestyl and O-tosyl group. 
     
     
       19. A process for preparing a compound of Formula IV 
       
         
           
           
               
               
           
         
       
       and its pharmaceutically acceptable salts, pharmaceutically acceptable enantiomers, diastereomers, N-oxides, wherein
 R 11  is hydrogen or fluoro, R 12  is fluoro, amide or sulphonamide derivatives and s represents 1 to 2;
 Z represents oxygen, sulphur, NR 10 , wherein R 10  represents hydrogen, C 1-6  alkyl; 
 Q represents (CH 2 ) n  wherein n represents 1 to 4, or CHR 8  wherein R 8  represents H, OH, C 1-6 , alkyl, alkenyl, alkoxy, or CH 2 CHR 9  wherein R 9  represents H, OH, lower alkyl (C 1 -C 4 ) or lower alkoxy (C 1 -C 4 ); and 
 
 R 4  represents a C 1 -C 15  saturated or unsaturated aliphatic hydrocarbon group in which from 1 to 6 hydrogen atoms may be substituted with the group independently selected from halogen, arylalkyl, arylalkenyl, heteroarylalkyl or heteroarylalkenyl having 1 to 2 hetero atoms selected from a group consisting of nitrogen, oxygen and sulphur atoms with an option that any 1 to 3 hydrogen atoms on the ring in said arylalkyl, arylalkenyl, hetero arylalkenyl group may be substituted with lower alkyl (C 1 -C 4 ), lower perhalo alkyl (C 1 -C 4 ), cyano, hydroxyl, nitro, lower alkoxycarbonyl, halogen, lower alkoxy (C 1 -C 4 ), lower perhaloalkoxy (C 1 -C 4 ), unsubstituted amino, N-lower alkylamino (C 1 -C 4 ), N-lower alkylamino carbonyl (C 1 -C 4 ), comprising: 
 (i) condensing a compound of Formula IX with a compound of Formula X 
 
       
         
           
           
               
               
           
         
          where Z, Q, R 11 , R 12  and s have the same meanings as defined earlier for Formula IV, to give a protected compound of Formula XI, 
       
       
         
           
           
               
               
           
         
         (ii) deprotecting the compound of Formula XI in the presence of a deprotecting agent to give an unprotected intermediate of Formula XII where Z, Q, R 11 , R 12 , s have the same meanings as defined earlier, and 
       
       
         
           
           
               
               
           
         
         (iii) the intermediate of Formula XII is N-alkylated or benzylated with a suitable alkylating or benzylating agent to give a compound of Formula IV wherein Z, Q, R 11 , R 12 , and s are the same as defined earlier; or 
         (b) (i) condensing a compound of Formula IX with a compound of Formula XIII 
       
       
         
           
           
               
               
           
         
          where Z, Q, R 4  and s have the same meanings as defined earlier for Formula IV; or 
         (c) (i) condensing a compound of Formula XIV with a compound of Formula X 
       
       
         
           
           
               
               
           
         
          where Z, Q and s have the same meanings as defined earlier for Formula IV, to give a protected compound of Formula XV, 
       
       
         
           
           
               
               
           
         
         (ii) deprotecting the compound of Formula XV in the presence of a deprotecting agent to give an unprotected intermediate of Formula XVI, wherein Z, Q and s have the same meanings as defined earlier, 
       
       
         
           
           
               
               
           
         
         (iii) N-alkylating or benzylating the intermediate of Formula XVI with a suitable alkylating or benzylating agent to give a compound of Formula XVI, wherein Z, Q, R 4  and s are the same as defined earlier, 
       
       
         
           
           
               
               
           
         
         (iv) reducing the compound of Formula XVII to give a compound of Formula XVII, wherein Z, Q, R 4  and s have the same meanings as defined earlier, and 
       
       
         
           
           
               
               
           
         
         (v) reacting a compound of Formula XVIII with acid chlorides to give a compound of Formula IV (R 11 =H, R 12 =substituted sulfonamide). 
       
     
     
       20. The process according to  claim 19  wherein P is a protecting group for an amino group and is selected from the group consisting of benzyl or t-butoxy carbonyl groups. 
     
     
       21. The process according to  claim 19  wherein the reaction of a compound of Formula IX with a compound of Formula X to give a compound of Formula XI, the reaction of a compound of Formula XIII with a compound of Formula IX or the reaction of a compound of Formula XIV with a compound of Formula X is carried out in the presence of a condensing agent which is selected from the group consisting of 1-(3-dimethyl aminopropyl)-3-ethyl-carbodiimide hydrochloride (EDC) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). 
     
     
       22. The process according to  claim 19  wherein the reaction of a compound of Formula IX with a compound of Formula X, the reaction of a compound of Formula XIII with a compound of Formula IX or the reaction of a compound of Formula XIV with a compound of Formula X is carried out at about 0-14° C. 
     
     
       23. The process according to  claim 19  wherein the deprotection of a compound of Formula XI to give a compound of Formula XII or the deprotection of a compound of Formula V to give a compound of Formula XVI is carried out with a deprotecting agent which is selected from the group consisting of palladium on carbon, trifluoroacetic acid (TFA) and hydrochloric acid. 
     
     
       24. The process according to  claim 19  wherein the N-alkylation or benzylation of a compound of Formula XII to give a compound of Formula IV or the N-alkylation or benzylation of a compound of Formula XVI to give a compound of Formula XVII is carried out with a suitable alkylating or benzylating agent, L-R 4 , wherein L is any leaving group and R 4  is the same as defined earlier. 
     
     
       25. The process according to  claim 24  wherein the leaving group is selected from the group consisting of halogen, O-mestyl and O-tosyl group. 
     
     
       26. The process according to  claim 19  wherein the reduction of a compound of Formula XVII to give a compound of Formula XVIII is carried out with triphenylphosphine. 
     
     
       27. The process according to  claim 19  wherein the acid chlorides used in the reaction of a compound of Formula XVIII with acid chlorides is selected from the group consisting of phenylacetyl chloride, 4-nitrophenylsulfonyl chloride, benzene sulfonyl chloride, benzyloxyacetyl chloride, 4-methoxyphenylsulfonyl chloride and 4-bromophenylsulfonyl chloride.